Seiger A, Nordberg A, von Holst H, Bäckman L, Ebendal T, Alafuzoff I, Amberla K, Hartvig P, Herlitz A, Lilja A
Department of Geriatric Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
Behav Brain Res. 1993 Nov 30;57(2):255-61. doi: 10.1016/0166-4328(93)90141-c.
We report on the clinical outcome of a first case of intracranial infusion of nerve growth factor (NGF) to an Alzheimer patient. The therapeutic attempt is based on animal research showing that NGF stimulates central cholinergic neurons of the type known to be lost during the development of Alzheimer's disease (AD). Furthermore, our own previous clinical experience of infusing NGF to support the survival of intracranially transplanted adrenal chromaffin cells to Parkinsonian patients indicate this approach to be technically possible and safe and clinically of significant potential. Our first case was a 69-year-old woman, with symptoms of dementia since 8 years. Intraventricular infusion of 6.6 mg NGF over three months resulted in a marked transient increase in uptake and binding of [11C]nicotine in frontal and temporal cortex and a persistent increase in cortical blood flow as measured by PET as well as progressive decreases of slow wave EEG activity. After one month of NGF infusion, tests of verbal episodic memory were improved whereas other cognitive tests were not. No adverse effects of the NGF infusion were found. The results of this single case indicate that NGF may counteract cholinergic deficits in AD, and suggest that further clinical trials of NGF infusion in AD are warranted.
我们报告了首例向阿尔茨海默病患者颅内输注神经生长因子（NGF）的临床结果。该治疗尝试基于动物研究，研究表明NGF可刺激已知在阿尔茨海默病（AD）发展过程中会丧失的中枢胆碱能神经元。此外，我们之前向帕金森病患者颅内移植的肾上腺嗜铬细胞输注NGF以支持其存活的临床经验表明，这种方法在技术上是可行且安全的，并且在临床上具有显著潜力。我们的首例患者是一名69岁女性，8年来一直有痴呆症状。在三个月内脑室内输注6.6毫克NGF导致额叶和颞叶皮质中[11C]尼古丁摄取和结合显著短暂增加，通过PET测量的皮质血流量持续增加，以及慢波脑电图活动逐渐减少。在输注NGF一个月后，言语情景记忆测试有所改善，而其他认知测试则没有。未发现NGF输注有不良反应。该单例结果表明，NGF可能抵消AD中的胆碱能缺陷，并提示有必要在AD中进一步开展NGF输注的临床试验。
